Prophylaxis with Antifungal Agents in Hematological Patients

Prophylaxis with antifungal agents reduces the risk of invasive fungal infection (IFI) in patients with hematological disorders, a recent study shows.

Letícia P. Leonart, MSc, from the Federal University of Paraná, Curitiba, Brazil, and colleagues, published the results of their systematic review and network meta-analysis online in the Journal of Clinical Pharmacy and Therapeutics.

IFIs represent a significant health problem in immunocompromised patients, especially in those with HIV infection or hematologic malignancies, or those who are hematopoietic stem cell transplant recipients. Candida albicans and Aspergillus fumigatus are among the most common causes of these infections.

“The mortality can exceed 50% in some patient populations, depending on the pathogen and the underlying condition or disease,” the authors write.

Yet, despite the variety of antifungal agents currently available to treat these infections, IFIs remain difficult to manage. Clinical practice guidelines provide conflicting recommendations, thus leading to decision-making challenges for clinicians as they manage patients with IFIs.

In addition, analyses of high-quality evidence on the efficacy and safety of antifungal agents, including from double-blind randomized controlled trials (RCTs), have been lacking. Dr. Leonart and colleagues therefore aimed to evaluate the safety and efficacy of different antifungal agents used for prophylaxis of IFI in patients with hematological disorders.

Their review and meta-analysis included only double-blind RCTs, to reduce the risk of bias in the analysis, and thus, strengthen the clinical evidence.

After electronic searches, they ultimately analyzed data from 25 RCTs evaluating amphotericin B (conventional and liposomal formulations), ketoconazole, fluconazole, itraconazole, micafungin, miconazole, nystatin, posaconazole, or voriconazole.

“The most common treatment was fluconazole (11 studies), followed by itraconazole (five studies),” the authors say. Of the 25 studies, 19 used placebo as a comparator for one of the antifungal drugs under evaluation, and the other six were head-to-head studies.

The researchers analyzed the studies and found that, overall, the azoles posaconazole and voriconazole were the most appropriate agents for IFI prophylaxis in patients with hematological disorders. Posaconazole was the most effective agent in reducing the incidence of IFI, and was the only one of those evaluated that showed superiority against placebo in reducing IFI-related mortality.

Furthremore, the researchers found that the azoles performed better than placebo for preventing invasive candidiasis in these patients. Voriconazole performed best, followed by posaconazole, the authors write.

The data also suggested that voriconazole performed best in preventing invasive aspergillosis in this patient population, followed by liposomal amphotericin B and posaconazole.

The authors acknowledge the limitations of their study, including that none of the studies evaluated involved caspofungin and anidulafungin, because none of the RCTs met the inclusion criterion of double-blinding. The different drug regimens and dosages used among the clinical trials also complicates determination of the best therapeutic option, they add.

Nevertheless, Dr. Leonart and colleagues emphasize that their findings were similar to those of previous studies. “The results of our work support prophylaxis with antifungal agents as reducing the risk of IFI in haematological patients. Overall, the second-generation azoles were found to be the best option for preventing IFI in this population,” they conclude.

Dr. Parry graduated from the University of Liverpool, England in 1997 and is a board-certified veterinary pathologist. After 13 years working in academia, she founded Midwest Veterinary Pathology, LLC where she now works as a private consultant. She is passionate about veterinary education and serves on the Indiana Veterinary Medical Association’s Continuing Education Committee. She regularly writes continuing education articles for veterinary organizations and journals, and has also served on the American College of Veterinary Pathologists’ Examination Committee and Education Committee.